title: Inhibitor scaffolds for 2-oxoglutarate-dependent histone lysine demethylases.
abstract: The dynamic methylation of histone lysyl residues plays an important role in biology by regulating transcription, maintaining genomic integrity, and by contributing to epigenetic effects. Here we describe a variety of inhibitor scaffolds that inhibit the human 2-oxoglutarate-dependent JMJD2 subfamily of histone demethylases. Combined with structural data, these chemical starting points will be useful to generate small-molecule probes to analyze the physiological roles of these enzymes in epigenetic signaling.
authors.affiliation: The Department of Chemistry and the Oxford Centre for Integrative Systems Biology, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Rose
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Ng
authors.forename: Jasmin
authors.initials: J
authors.lastname: Mecinović
authors.forename: Benoît M R
authors.initials: BM
authors.lastname: Liénard
authors.forename: Simon H
authors.initials: SH
authors.lastname: Bello
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.forename: Michael A
authors.initials: MA
authors.lastname: McDonough
authors.forename: Udo
authors.initials: U
authors.lastname: Oppermann
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
mesh_terms: D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007656:Ketoglutaric Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007656:Ketoglutaric Acids; D010089:Oxidoreductases, N-Demethylating